This invention relates to novel intravenous solutions for influencing renal function and for follow-up maintenance therapy. An intravenous solution of the invention is more particularly for treating altered renal function or for prophylactically conditioning the kidney to resist that the kidney enters a condition of altered renal function. The term altered renal function as employed herein means a qualitatively and quantitatively depleted or insufficient production of urine, insufficient clearance of metabolic and toxic substances normally cleared by the kidney such as electrolytes, urea, creatinine, phosphates, endogenous and exogenous toxins, pharmaceuticals and their metabolites, a depleted or insufficient ability of the kidney to acidify the urine by excretion of non-volatile or strong acids, or a depleted or insufficient capability of the kidney to produce bicarbonate and thus inability of the kidney to maintain a metabolic acid-base balance within acceptable limits. In such conditions, the therapy normally involves administration of diuretics, preferably loop diuretics, to encourage diuresis.
The intravenous solution of the invention in general finds application in treating patients preliminary to, during and after surgical intervention or any other condition or treatment which may lead to altered renal function. Examples of treatment with potentially nephrotoxic substances include contrast media, antibiotics, cytostatics, cytotoxic drugs, and immuno suppressive drugs. A wide variety of solutions, some being described as substitution fluids are employed for intravenous administration. Commonly used solutions and their compositions are shown in the following Table I:
TABLE I __________________________________________________________________________ Concentrations Ionic concentration mval/liter Solution Solute g/100 ml (Na.sup.+) (K.sup.+) (Ca.sup.2+) (Cl.sup.-) (HCO.sub.3.sup.-) __________________________________________________________________________ Dextrose in water 5.00% Glucose 5.00 -- -- -- -- -- 10.00% Glucose 10.00 -- -- -- -- -- Saline Hypotonoc (0.45%, NaCl 0.45 77 -- -- 77 -- half normal) Isotonic (0.9%, NaCl 0.90 154 -- -- 154 -- normal) Hypertonic NaCl 3.00 513 -- -- 513 -- 5.00 855 -- -- 855 -- Dextrose in saline 5% in 0.22% Glucose 5.00 -- -- -- -- -- NaCl 0.22 38.5 -- -- 38.5 -- 5% in 0.45% Glucose 5.00 -- -- -- -- -- NaCl 0.45 77 -- -- 77 -- 5% in 0.9% Glucose 5.00 -- -- -- -- -- NaCl 0.90 154 -- -- 154 -- Ringer's NaCl 0.86 KCl 0.03 147 4 5 156 -- CaCl.sub.2 0.03 Lactated Ringer's NaCl 0.60 KCl 0.03 CaCl.sub.2 0.02 130 4 3 109 28 Na lactate 0.31 0.31 Hypertonic sodium NaHCO.sub.3 5.00 595 -- -- -- 595 bicarbonate (0.6 M) Hypertonic sodium NaHCO.sub.3 7.50 893 -- -- -- 893 bicarbonate (0.6 M) Potassium chloride KCl 14.85 -- 211 -- 2 __________________________________________________________________________
Administration of the Dextrose solutions is physiologically equivalent to the administration of distilled water since glucose is rapidly metabolized to CO.sub.2 and H.sub.2 O. The Dextrose is however essential to render the solution isotonic and thus avoid hemolysis. The Saline solutions are most commonly administered since most patients in need of treatment are not only water-depleted but also Na.sup.+ depleted, i.e. salt-depleted.
The plasma Na.sup.+ concentration can be employed to assist in determining which of the above Dextrose, Saline or Dextrose in Saline solutions is most appropriate. The Dextrose solutions provide a small amount of calories, for example the 5% Dextrose or 5% Dextrose in 0,22% saline is equivalent to 200 kcal per liter of solution.
The Ringer's solutions comprised in the above Table include physiologic amounts of K.sup.+ and Ca.sup.++ in addition to NaCl. The lactated Ringer's solution comprising 28 mEq of lactate per liter (which metabolizes to HCO.sub.3.sup.-) has a composition close to that of extracellular fluid.
The hypertonic Sodium bicarbonate solutions are primarily employed in the treatment of metabolic acidosis for example by administration of a 7.5% or higher solution comprised in 50 ml ampuls, but can be added to other intravenous solutions, however not including the Ringer's solutions since precipitation of the HCO.sub.3.sup.- with the Ca.sup.++ would take place. Similarly, the Potassium Chloride solution can be added to other intravenous solutions, but care needs to be taken not to intravenously administer any concentrated solution of K.sup.+ since this can produce an excessive or too rapid increase in plasma concentration of K.sup.+, which can be fatal.
Other than the above-mentioned hypertonic Sodium bicarbonate solutions, none of the above solutions are known to have any specific influence on kidney function. The hypertonic Sodium bicarbonate solutions on the other hand are normally administered only in limited quantities, at most in quantities sufficient to temporarily correct, normally only in part, a condition of metabolic acidosis. Suggestions to intravenously administer higher quantities of the available Sodium bicarbonate solutions has met with understandable resistance in view particularly of the fact that such solutions are strongly hypertonic and all comprise very much more than or less than physiological amounts of cation solute. Thus, for example the above-mentioned higher concentration 7.5% Sodium bicarbonate solution available in 50 ml ampuls comprises about 900 mval of Na.sup.+, and 900 mval of HCO.sub.3.sup.- per liter of solution which is neither physiological for Na.sup.+ nor for HCO.sub.3.sup.-. In contrast, the normal value for Na.sup.+ in the blood is from 135 to 146 mval/liter and the normal value for HCO.sub.3.sup.- is 22 to 26 mval/liter.